Background: Epilepsy is a common neurological condition which affects between 0.5% and 1% of the population. Approximately 30% of people with epilepsy do not respond to treatment with currently available drugs. The majority of these people have partial epilepsy. Vigabatrin is an antiepileptic drug licensed for use in the treatment of refractory epilepsy. No major side effects associated with the use of vigabatrin were detected by initial randomised controlled trials of the drug. However, longer-term observational studies have subsequently identified that its use is associated with asymptomatic visual field constriction.
Objectives: The objective of this review was to synthesise evidence from short-term, randomised, placebo-controlled trials of vigabatrin. We summarised the effects of vigabatrin on seizures and short-term side effects when used as an add-on treatment for people with drug-resistant partial epilepsy. A review of longer-term observational studies and estimates of proportions of patients developing visual field constrictions is currently being undertaken and results will be cited in this review in due course.
Search methods: We searched the Cochrane Epilepsy Group Specialised Register (12 October 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 9), MEDLINE (1946 to October week 1, 2012) and reference lists of articles. We also contacted the manufacturers of vigabatrin (Hoechst Marion Roussel).
Selection criteria: We included randomised, double-blind, placebo-controlled, fully published trials of vigabatrin in people with drug-resistant partial epilepsy.
Data collection and analysis: Two review authors assessed trials for inclusion and extracted data. Primary analysis was by intention-to-treat (ITT). Outcomes evaluated included 50% or greater reduction in seizure frequency, treatment withdrawal and side effects observable in the short term. Results are presented on the risk ratio (RR) scale with 95% or 99% confidence intervals (CI).
Main results: Eleven suitable trials that tested vigabatrin doses between 1000 mg and 6000 mg were identified and included in the analysis. There were 982 observations on 747 patients in the primary ITT analysis of treatment efficacy. Patients treated with vigabatrin were significantly more likely to obtain a 50% or greater reduction in seizure frequency compared with those treated with placebo (RR 2.58, 95% CI 1.87 to 3.57). Those treated with vigabatrin were also significantly more likely to have treatment withdrawn (RR 2.49, 95% CI 1.05 to 5.88), and were more likely to experience a number of side effects, significantly so for fatigue or drowsiness. There was some evidence of small study effect bias, with smaller studies tending to report greater estimates of RR than larger studies. It is possible, therefore, that the actual RR of obtaining 50% reduction in seizure frequency is less than that obtained by a meta-analysis of fully published studies.
Authors' conclusions: This review of randomised controlled trials showed that vigabatrin can reduce seizure frequency in people with drug-resistant partial epilepsy. Short-term follow-up of patients showed that some side effects were associated with its use. Further analysis of longer-term observational studies is required to evaluate how likely patients are to develop visual field defects and whether such side effects are associated with dose and duration of drug use.